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Biomedical subjects

T H Jones

Publications and source records attributed to T H Jones.

At least 55 records · Page 3Linked to original sources
PubMed2000

Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms.

AIMS: High androgen levels are presumed by many to explain the male predisposition to coronary artery disease. However, natural androgens inhibit male atherosclerosis(1). Our aim was to determine whether levels of androgens differ between men with and without coronary artery disease. METHODS AND RESULTS: Ninety male subjects (60 with positive, and 30 with negative coronary angiograms) were recruited. Early morning, fasting blood samples were taken from each patient and free, total and bioavailable testosterone, sex hormone binding globulin, oestradiol, and lipids were measured. Bioavailable testosterone was assayed using a modified technique. Free androgen index was calculated. Men with coronary artery disease had significantly lower levels of free testosterone (mean (standard deviation)); 47.95 (13.77) vs 59.87 (26. 05) pmol. l(-1), P=0.027), bioavailable testosterone; 2.55 (0.77) vs 3.26 (1.18) nmol. l(-1), P=0.005 and free androgen index; 37.8 (10. 4) vs 48.47 (18.3), P=0.005, than controls. After controlling for differences in age and body mass index the differences in free androgen index and bioavailable testosterone remained statistically significant (P=0.008 and P=0.013, respectively). CONCLUSION: Men with coronary artery disease have significantly lower levels of androgens than normal controls, challenging the preconception that physiologically high levels of androgens in men account for their increased relative risk for coronary artery disease.

Adult↗
PubMed2000

Aging reduces the responsiveness of coronary arteries from male Wistar rats to the vasodilatory action of testosterone.

This study was performed to examine whether aging affects the vasodilatory effects of testosterone in the coronary arteries of male rats. Isolated coronary arteries from young mature (3-4 months) and elderly (22-26 months) male Wistar rats were studied in a wire myograph. Contractile function and endothelial function were assessed by measuring vasomotor responses to 10-100 mmol/l KCl, 0.1 mmol/l prostaglandin F(2alpha) (PGF(2alpha)) and 10 micromol/l acetylcholine. Sensitivity to the vasodilatory effects of testosterone was assessed by constructing dose-response curves to concentrations between 1 micromol/l and 1 mmol/l testosterone dissolved in water in vessels maximally preconstricted with PGF(2alpha). The compliance characteristics of each vessel and serum testosterone levels from each animal were measured. Histological sections of myocardium were examined for differences in coronary artery morphology. Vessels from elderly animals were significantly more resistant to the vasodilatory effects of testosterone than vessels from young animals (P=0.001 by analysis of covariance). Vessels from elderly animals were also significantly less compliant (7.32+/-0.43 microm/mN, compared with 10.99+/-1.52 microm/mN in young animals; P=0.011), and the levels of circulating testosterone in elderly animals were lower, but not significantly so (2.04+/-0.63 nmol/l compared with 3.88+/-1.7 nmol/l; P=0.32). Vessels from elderly animals were less contractile in response to KCl than those from young animals (P=0.004 by analysis of covariance). There were no significant differences between the two groups in their responses to PGF(2alpha) or acetylcholine. Thus it is concluded that coronary arteries from elderly rats are significantly less sensitive to the vasodilatory effects of testosterone than those from young animals.

Acetylcholine↗
PubMed1999

Ammonia chemical ionization tandem mass spectrometry in structure determination of alkaloids. I. Pyrrolidines, piperidines, decahydroquinolines, pyrrolizidines, indolizidines, quinolizidines and an azabicyclo[5.3.0]decane.

CI-MS/MS of alkaloids with ammonia reagent gas and collision-induced dissociation provides unique structural information for certain mono- and bi-cyclic alkaloids. This technique was applied to solve the structures of 195C, a 4,6-disubstituted quinolizidine alkaloid found in frog skin and an ant, and 275A, a novel 3,5-disubstituted azabicyclo[5.3.0]decane found in frog skin.

Alkaloids↗
PubMed1999

3-methyl-4-phenylpyrrole from the ants Anochetus kempfi and Anochetus mayri.

The cephalic extracts of the ant Anochetus kempfi were found to contain 2,5-dimethyl-3-isoamylpyrazine (1) and 3-methyl-4-phenylpyrrole (2). The structures of these compounds were established from their spectral data and by comparison with synthetic samples. This is the first report of a phenylpyrrole found in an insect and only the third report of a pyrrole from ants.

Animals↗
PubMed1999

A high uptake eye and foot screening service for an urban population.

AIMS: A community diabetes eye screening service using slit-lamp biomicroscopy and colour fundus photography was set up in 1993 at the Barnsley District General Hospital Diabetes Centre with a foot screening service being added in 1994. The service is available for all diabetic patients in the Barnsley health district (encompassing 220,000 people). After 4 1/2 years, a survey was carried out to establish the uptake of this service. METHODS: All diabetic patients on the local diabetes register were checked for attendance at the eye screening service or the Barnsley District General Hospital Eye Department. Questionnaires were sent to general practitioners to establish what screening was received by those attending neither of these services. RESULTS: More than 10% of patients were found to be incorrectly registered. Of the 4000 correctly registered diabetic patients, 62% were screened annually by this service and 25% were under the care of the Department of Ophthalmology. Half of the remaining 13% were screened at other hospitals or by opticians or general practitioners and the other half were either too old or ill to be screened or were non-compliant. CONCLUSIONS: This service has a high uptake, and is recommended for a circumscribed urban population.

Diabetes Complications↗
PubMed1999

Purification and characterization of a novel dipeptidyl peptidase from Dictyostelium discoideum.

A dipeptidyl peptidase (DPP) was purified to homogeneity using lys-ala-beta-naphthylamide, the standard substrate for DPP II. The enzyme is a monomer with a Mr of 70kDa, pl 5.2, and Km 5.0 microM. Its terminal amino acid sequence was XXLLYAIQKRLF and was not identical to that of any known protein. Although initially considered to be a DPP II, the enzyme differed in some properties from classical DPP IIs. It had a pH optimum of 7.9, was not active on X-pro-naphthylamides, the usual substrates of mammalian DPP II, but was active on arg-arg- and asp-arg-naphthylamides, substrates acted on by the DPP III class of enzymes. This enzyme therefore combines properties typical of both DPP II and III and differs from all previously described DPPs. Activity on lys-ala-beta-naphthylamide was most abundant during aggregation and its activity is consistent with processing specific peptides during development.

Aminopeptidases↗
PubMed1999

Purification and characterization of tripeptidyl peptidase I from Dictyostelium discoideum.

A tripeptidyl peptidase I from Dictyostelium discoideum was purified 744-fold to near homogeneity. The enzyme is 214 kDa in size and is composed of two monomers with a M(r) of 107 kDa. It has two pH optima at pH 4.5 and 5.9 and is a serine peptidase with no aminopeptidase or dipeptidyl peptidase activity. The enzyme was relatively specific showing activity on ala-ala-phe-p-nitroaniline but also acted on substrates with proline in the P1 position in contrast to mammalian TPP I. The K(m) values of the enzyme at pH 4.5 for ala-ala-phe-, ala-phe-pro- and ala-ala-pro-p-nitroanilines were 27 microM, 437 microM and 888 microM, respectively. The enzyme is most abundant during the amoeba stage of the life cycle but is present in the early stages of development and may therefore have a dual role in the organism in mobilizing amino acids or in processing specific peptides or proteins.

Aminopeptidases↗
PubMed1999

IL-8 mRNA expression by in situ hybridisation in human pituitary adenomas.

Several cytokines have been shown to be expressed in normal and adenomatous pituitary tissue. Recently, interleukin-8 (IL-8) mRNA was identified by reverse transcription (RT)-PCR in each of a series of 17 pituitary tumours examined. We have investigated further the presence of IL-8 mRNA, using in situ hybridisation in two normal human anterior pituitary specimens and 25 human pituitary adenomas. IL-8 mRNA was not identified in either of the two normal pituitary specimens. Only three of the 25 adenomas were positive for IL-8 mRNA. In these three tumours, which included two null cell adenomas and one gonadotrophinoma, the majority of tumour cells (>90%) were positive for IL-8 mRNA. The remaining 22 adenomas were completely negative. There was no difference in tumour size or type between the IL-8 positive and the IL-8 negative tumours, and immunocytochemistry for von Willebrandt factor showed that the two groups were also similar in their degree of vascularisation. In conclusion, IL-8 mRNA was found in 12% of pituitary adenomas studied and was histologically identified within the tumour cells. In situ hybridisation is a more appropriate technique for assessing cytokine mRNA production by human pituitary tumours because RT-PCR may be too sensitive, identifying very small, possibly pathologically insignificant, quantities of mRNA that could be produced by supporting cells such as fibroblasts, endothelial cells or macrophages.

Adenoma↗
PubMed1998

Endocrine-mediated mechanisms of fatigue during treatment with interferon-alpha.

Fatigue occurs in more than 70% of patients treated with interferon-alpha (IFN-alpha) and is the most problematic toxicity associated with IFN-based immunotherapy. Abundant evidence suggests that immune-mediated endocrine disease occurs during IFN-alpha therapy, which may contribute to the etiology of fatigue. Autoimmune thyroid disease is a well-recognized consequence of IFN-alpha therapy and may be mediated by the induction of IFN-gamma production by lymphocytes. Administration of exogenous IFN-gamma has been associated with upregulation of class II major histocompatibility antigens in the thyroid and the development of thyroiditis. Interferon-alpha also stimulates the production of interleukin-6; both interleukin-6 and IFN-gamma have specific effects on thyrocyte function. There also is evidence suggesting that IFN-alpha initiates a cytokine cascade that effects the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, thus affecting regulation of glucocorticoid and sex steroid hormone secretion, but the clinical significance of these observations has not been established. Although endocrine disease will not explain the occurrence of fatigue symptoms in all patients, there is clear evidence that hormonal deficiency syndromes occur in a relatively large portion of patients receiving systemic IFN-alpha therapy. Most importantly, the possibility of hypothyroidism must be considered; however, diagnosis of hypothyroidism in cancer patients is complicated by the occurrence of the "sick euthyroid syndrome." Clinical recommendations for assessment and treatment of IFN-alpha-induced fatigue are offered. Most importantly, measurements of thyroid-stimulating hormone and antithyroid autoantibodies should be used to evaluate thyroid status. Acknowledging the limitations of current clinical data, adrenal- and gonadal-axis dysfunction also must be considered in patients with IFN-alpha-induced fatigue.

Endocrine System Diseases↗
PubMed1997

Effect of interleukin-1 and dexamethasone on interleukin-6 production and growth in human meningiomas.

Interleukin-6 (IL-6) has been shown to be released by cultured human meningioma cells and may be a positive or negative regulator of tumour growth. IL-6 protein and mRNA levels have been examined in a series of meningiomas. In 14 cases, the results are compared with the effects of IL-6 and dexamethasone on growth and IL-6 secretion in vitro. Tumours with the highest in vivo IL-6 mRNA expression also showed maximum induction of IL-6 and increased cellular proliferation on IL-1 stimulation in vitro. Dexamethasone decreased the IL-1-stimulated IL-6 release in all cases. Meningiomas which had little or no IL-6 message were refractory to IL-1 control of IL-6. Remarkably, these formed the group of meningiomas that increased their growth rate in response to dexamethasone.

Adult↗
PubMed1997

Cuticular extracts of five common mantids (Mantodea:Mantidae) of the eastern United States.

We undertook a preliminary investigation of the cuticular extracts of five common mantid species in the eastern United States: Tenodera sinensis (Saussure), T. angustipennis (Saussure) and Mantis religiosa (Linnaeus) introduced from the Old World and Stagmomantis carolina (Johannson) and Bruneria borealis (Scudder), which are New World species. The major components of these mixtures were normal alkanes, predominately hentriacontane, or in the case of the parthenogenic species B. borealis, tritriacontane. Tricontanal was detected in the extracts of all five species, and smaller amounts of other aldehydes and n-tricontanol were detected in some species. Complex mixtures of methyl and dimethylalkanes also were present in these extracts. The composition of the cuticular hydrocarbons of these mantids may be an adaptation for reduction of evaporative water loss in these insects that inhabit open fields.

Alkanes↗
PubMed1997

Treatment of isolated hypogonadotropic hypogonadism effect on bone mineral density and bone turnover.

Isolated hypogonadotropic hypogonadism (IHH) presents with delayed puberty in the late teens or early twenties, with a period of testosterone deficiency during active growth. The aims of the study were to determine 1) whether long term treatment of IHH results in normalization of bone density (BMD) and bone turnover, and 2) whether BMD and bone turnover respond to increasing doses of hCG. We studied 10 men, aged 26-46 yr, with IHH who were treated with hCG or testosterone esters (Sustanon) for 2-22 yr, with age at the start of treatment between 17-29 yr, and 10 age- and body weight-matched normal men as a control group. At baseline, lumbar spine, femoral neck, trochanter, and Ward's triangle BMD values were decreased, and serum bone Gla-protein, bone alkaline phosphatase, and urinary pyridinoline, deoxypyridinoline, and N-terminal telopeptide of type I collagen were increased compared with control values (by paired t test, P = 0.02, 0.03, 0.01, 0.05, 0.002, 0.02, 0.02, 0.007, and 0.006, respectively). The age at initial therapy was significantly correlated with total body BMD (r = -0.73; P = 0.017) and lumbar spine BMD (r = -0.756; P = 0.0097). Serum free testosterone was correlated with total body and trochanter BMD (r = 0.635; P = 0.048 and r = 0.629; P = 0.05), and serum free estradiol was correlated with total body and trochanter BMD (r = 0.641; P = 0.045 and r = 0.634; P = 0.048). Six of the 10 patients were recruited for a longitudinal study in which the dose of hCG was increased monthly from 2000 i.u. twice per week to 6000 i.u. twice per week. After increasing doses of hCG, levels of serum testosterone and estradiol and total body BMD increased significantly (by paired t test P = 0.001, 0.003, and 0.01, respectively). Serum bone Gla-protein levels increased by the first month and then decreased (paired t test, corrected by Bonferroni's method). Serum bone alkaline phosphatase and urinary N-terminal telopeptide of type I collagen/creatinine levels decreased significantly after increasing the dose of hCG. We conclude that patients with IHH who have serum testosterone within the laboratory reference range may require a higher dose of hCG to normalize BMD and bone turnover.

Adult↗
PubMed1997

Suppression of tyrosine kinase activity inhibits [3H]thymidine uptake in cultured human pituitary tumor cells.

Tyrosine kinases are involved in the phosphorylation of proteins that regulate cell growth and proliferation. The mitogenic effect of several growth factors requires tyrosine kinase activity of their receptors. The effect of inhibition of tyrosine kinase activity on thymidine uptake into cultured human pituitary adenoma cells was studied using two inhibitors, genestein and methyl-2,3-dihydroxycinnamate (MDHC). Of 33 pituitary adenomas, 7 incorporated sufficient [3H]thymidine to be investigated in the experiments. Genestein and MDHC both potently inhibited thymidine uptake into these tumors, with a mean inhibition by 74 mumol/L genestein of 61.96 +/- 18.96% (+/- SD inhibition of basal), by 740 mumol/L genestein of 92.65 +/- 8.59%, and by 100 mumol/L MDHC of 93.84 +/- 3.85%. The 7 pituitary adenomas were all large with suprasellar extension and secreted interleukin-6 in vitro. They included 2 prolactinomas, 1 somatotropinoma, 1 mammosomatropinoma, and 3 clinically nonfunctioning adenomas. Epidermal growth factor stimulated thymidine uptake in 2 of the 3 clinically nonfunctioning adenomas studied, and this stimulation was inhibited by genestein. Both of these tumors released FSH in cell culture and are probably silent gonadotropinomas. The growth stimulatory effect of conditioned medium from human pituitary cell culture on GH3 cells was inhibited by both genestein and MDHC. We conclude that tyrosine kinase activity is crucial for the integrity and growth of pituitary adenomas in culture. Growth factors released by pituitary adenomas potentially may maintain and promote tumor growth by stimulating tyrosine kinase activity.

Adenoma↗
PubMed1997

Effect of glucocorticoids and oestrogen on interleukin-6 production by human thyrocytes from patients with Graves' disease and toxic multinodular goitre and from HTori3 cells.

Interleukin-6 (IL-6) is a cytokine released by thyrocytes and is involved in disease processes such as autoimmune thyroid disease. The secretion of IL-6 can be stimulated by interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF), serum, TSH and agents which increase intracellular cyclic AMP levels. Antithyroid drugs such as methimazole inhibit IL-6 production by thyrocytes but the effects of glucocorticoids and oestrogen have not been investigated. The effects of dexamethasone and 17 beta-oestradiol on IL-1-, TNF-, TSH-, forskolin- and phorbol 12-myristate 13-acetate (PMA)-stimulated IL-6 release in serum-free conditions were studied in human thyrocytes derived from patients with Graves' disease and toxic multinodular goitres, and in the immortalised human thyrocyte cell line, HTori3. Dexamethasone inhibited IL-6 production under stimulated conditions. In serum-free conditions, no basal release of IL-6 was assayable. In all but one of the primary thyroid cultures, TSH did not stimulate IL-6 release above the lower detectable limit of the assay. In Graves' and multinodular goitre thyrocytes, inhibition of IL-1 (100 U/ml)-stimulated IL-6 release by dexamethasone (100 nmol/l) was 62.51% +/- 10.43 (S.E.M.), and in HTori3 cells it was 78.35% +/- 3.9. The degree of IL-1 stimulation of IL-6 release and inhibition by dexamethasone was not significantly different in thyrocytes derived from either Graves' or multinodular glands. 17 beta-Oestradiol had no effect on IL-1-stimulated IL-6 release in either primary thyroid cell culture or in HTori3 cells.

Cell Line, Transformed↗
PubMed1996

Primary tetradecenyl amines from the ant Monomorium floricola.

In contrast to other ants in the genus Monomorium that produce cyclic amines, extracts of Monomorium floricola contain (Z)-7-tetradecenylamine (1) and (Z)-9-tetradecenylamine (2). The structures of these compounds were established from their spectral data and by comparison with synthetic 2.

Acetylation↗